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Alk5 MEDIATED TGF-! SIGNALING ACTS UPSTREAM OF FGF10 TO REGULATE THE
PROLIFERATION AND MAINTENANCE OF DENTAL EPITHELIAL STEM CELLS
by
Sha Li
A Thesis Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(CRANIOFACIAL BIOLOGY)
May 2011
Copyright 2011 Sha Li

Mouse incisors grow continuously throughout life. This growth is supported by the division of dental epithelium stem cells that reside in the cervical loop of the incisor. Little is known about the maintenance and regulatory mechanisms of the dental epithelium stem cells compartment. In the present study, we investigated how TGF-β signal mediated mesenchymal-epithelial interactions control dental epithelium stem cells. We designed two approaches using incisor organ culture and BrdU pulse-chase experiments to identify and evaluate stem cell functions. We showed that loss of TGF-β type I receptor (Alk5) in the cranial neural crest derived dental mesenchyme severely affects the proliferation of transit amplifying (TA) cells and the maintenance of dental epithelium stem cells. Incisors of Wnt1-Cre;Alk5fl/fl mice lost their ability to continue to grow in vitro. The number of BrdU label retaining cells (LRC) was dramatically decreased in Alk5 mutant mice. Fgf10, Fgf3 and Fgf9 signaling in the dental mesenchyme were down regulated in Wnt1-Cre;Alk5fl/fl incisors. Strikingly, the addition of exogenous FGF10 into cultured incisors rescues dental epithelial stem cells in Wnt1-Cre;Alk5fl/fl mice. Therefore, we propose that Alk5 functions upstream of Fgf10 to regulate TA cell proliferation and stem cell maintenance, and this signaling mechanism is crucial for stem cell mediated tooth regeneration.

Alk5 MEDIATED TGF-! SIGNALING ACTS UPSTREAM OF FGF10 TO REGULATE THE
PROLIFERATION AND MAINTENANCE OF DENTAL EPITHELIAL STEM CELLS
by
Sha Li
A Thesis Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(CRANIOFACIAL BIOLOGY)
May 2011
Copyright 2011 Sha Li